Magnetic resonance imaging (MRI) is a powerful noninvasive technique that provides high quality three dimensional images of tissues, including information on anatomy, function, and metabolism of tissue in vivo.
The chelated Gd3+ metal ion improves image contrast by decreasing the longitudinal relaxation time (T1) of proximal water protons, which appear brighter in the T1-weighted MR image. Current advanced medical diagnosis techniques stipulate high-resolution images with a high magnetic field scanner.
However, current Gd3+-based contrast agents are incapable of meeting requirements as they do not have optimal relaxivity profiles at high magnetic fields. This requirement drives the research for smart contrast agents with high relaxivities (r1) for better tissue contrast at high magnetic fields and non-covalent binding affinity for human serum albumin (HSA) to enhance in vivo retention time in MR angiography applications.
In recent years, research has been conducted to develop contrast agents that have high pH sensitivity as well as meet the above requirements. pH sensitivity is a very important factor in in vivo mapping of living cells, particularly pathogenic cells.
Among the several approaches, the gadolinium complex into self-assembled nanoparticle system is one of the attractive approaches to develop high relaxivity contrast agent. In this system the high relaxivity achieved due to additive effect of self-aggregated Gd-complexed nuclei and slow global rotational motion.
Most of the gadolinium complexes reported to date have relaxivities lying between 20 and 25 mM−1s−1 at 20 MHz (0.47 T) in water at 25° C. Recently, Bota et. al. reported DOTA-based amphiphile with highest relaxivity of 34.8 mM−1s−1 at 25° C., 20 MHz (0.47 T) at pH 7.2.
There has recently been an increasing demand for pH-responsive contrast agents. Particularly, in in vivo pH mapping of tissues, pH-responsive contrast agents are very important in the diagnosis of cancers such as melanoma whose extracellular pH (pHe) is lower by almost 0.6 than that of healthy subcutaneous tissue. However, to the best of our knowledge, MRI contrast agents have not yet been developed that have high relaxivity and meet requirements in terms of relaxivity, pH sensitivity, and stability.